NHC‐gold(I) based catalysts have displayed outstanding results toward hydroalkoxylation of terminal and internal alkynes in solvent‐free conditions and using low catalyst loadings. It has been demonstrated that, in the hydrophenoxylation reaction the gold complex is composed by two moieties that determine the rate of the reaction by activating both substrates synergistically, i.e. [Au(OR)(NHC)] and [Au(η2‐alkyne)(NHC)]+. Then, these bimetallic systems act cooperatively toward the hydroalkoxylation reaction. Herein, density functional theory studies were carried out to get insights on the mechanism of hydrophenoxylation. The rate‐determining step, which corresponds to the formation of the C(alkyne)–O(alcohol) bond between [Au(OR)(NHC)] and [Au(η2‐alkyne)(NHC)]+, was studied using energy decomposition analyses (EDA). It was found that the C–O bond shows strong electrostatic and orbital interactions between both fragments in the homobimetallic, heterobimetallic and monogold mechanisms. Moreover, the analyses were expanded to copper and argentum, and the steric sensibility was also studied through the use of different NHC ligands, including IMes, IMe, SIMes, IPr, and IPr*, that differ on their steric demand.
Abstract:We have studied the influence of implicit solvent models, inclusion of explicit water molecules, inclusion of vibrational effects, and density functionals on the quality of the predicted pK a of small amino acid sidechain models. We found that the inclusion of vibrational effects and explicit water molecules is crucial to improve the correlation between the computed and the experimental values.However, achieving convergence of the results requires the addition of too many explicit water molecules, which generate new problems related to the presence of multiple minima in the potential energy surface. It thus appears that a satisfactory ab initio prediction of amino acid sidechain pK a will require methods that fully sample the potential energy surface in the presence of large solvation shells, while at the same time computing vibrational contributions to the enthalpy and entropy of the system under study in all points of that surface. Pending development of efficient algorithms for those computations, we strongly suggest that whenever abnormal protonation states are found in a computational study the reaction profile should be computed under the each of the different protonation micro-states by constraining the relevant N-H or O-H bonds, in order to avoid artifacts inherent to the complex nature of the factors contributing to the pK a .
The functionalization of alkynes by Au (N-heterocyclic carbene, NHC) complexes via the hydrophenoxylation reaction is a paradigm for the discussion between mono and dual metal catalysis. With the aim of mimicking the framework containing two gold units, achieved with molecular boxes, two NHC ligands were joined here with a chelated chain and this motif was examined in the hydrophenoxylation/hydroalkoxylation reactions through DFT calculations. This synthetic motif transforms the standard hydrophenoxylation intermolecular reaction from an inter-into an intra-molecular nucleophilic attack, when forming the C-O bond. Various chain lengths were tested with regard to the coordination of the alkyne to the cationic NHC-gold(I) center.
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